进展性双侧延髓内侧梗死的临床特征

目的探讨进展性双侧延髓内侧梗死(BMMI)的临床特征。 方法选择2021年12月14日和2022年5月9日经复旦大学附属中山医院青浦分院神经内科确诊的2例进展性BMMI患者的临床资料，总结BMMI的诊断学特征，并复习相关文献。 结果患者均为男性，年龄分别为50岁、40岁，病例1患者首发症状为头晕，病例2患者首发症状为头晕伴头颈疼痛。2例患者均于发病12 h内进展出现偏侧肢体乏力，并且在第2天偏侧肢体乏力进一步加重；随着病情进展，2例患者均出现构音障碍、吞咽困难；病例1患者在发病后1周出现四肢瘫痪。2例患者头颅磁共振成像(MRI)表现为双侧延髓内侧沿中线向背侧延伸的弥散加权成像(DWI)高信号病灶，外观类似"心"形或"Y"形，均确诊为BMMI。 结论BMMI典型的临床表现为四肢瘫痪、吞咽困难、构音障碍、深感觉障碍等，该病首发症状多不典型，应尽早完善头颅MRI检查有利于早期诊断和指导治疗。     

Design,synthesis, and biological evaluation of novel NO-releasing 4-chromanone derivatives as potential vasodilator agents

The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway is an effective mechanism involved in the treatment of hypertension. In our search for potential antihypertensive agents, a series of novel NO-donor derivatives of the 4-chromanone skeleton were designed and synthesized by coupling furoxans or nitrooxy NO-donor moieties. All derivatives showed enhanced nitric oxide releasing capacity and vasodilator activity with EC₅₀ values ranging from 0.0215 μM to 1.46 μM, obviously superior to those of precursor 3 . These biological evaluations indicated that all compounds displayed an important vasorelaxant effect, and several compounds (9c, 14b, 14c, 14d) presented good vasodilator activity, with 14c being the best. Furthermore, molecular modeling studies revealed that compound 14c occupied the pocket well with the phosphodiesterase 5 domain in a favorable conformation. In conclusion, we observed that these novel compounds can act as structural templates for the design and subsequent development of new vasodilators and antihypertensive drugs.     

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm,multicenter, prospective study

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.     

Crizotinib-based proteolysis targeting chimera suppresses gastric cancer by promoting MET degradation

As one of the common malignant cancer types, gastric cancer (GC) is known for late-stage diagnosis and poor prognosis. Overexpression of the receptor tyrosine kinase MET is associated with poor prognosis among patients with advanced stage GC. However, no MET inhibitor has been used for GC treatment. Like other tyrosine kinase inhibitors that fit the “occupancy-driven” model, current MET inhibitors are prone to acquired resistance. The emerging proteolysis targeting chimera (PROTAC) strategy could overcome such limitations through direct degradation of the target proteins. In this study, we successfully transformed the MET-targeted inhibitor crizotinib into a series of PROTACs, recruiting cereblon/cullin 4A E3 ubiquitin ligase to degrade the MET proteins. The optimized lead PROTAC (PRO-6 E) effectively eliminated MET proteins in vitro and in vivo, inhibiting proliferation and motility of MET-positive GC cells. In the MKN-45 xenograft model, PRO-6 E showed pronounced antitumor efficacy with a well-tolerated dosage regimen. These results validated PRO-6 E as the first oral PROTAC for MET-dependent GC.     

前列腺癌相关肿瘤标志物的研究进展

前列腺癌与其他恶性肿瘤一样,应争取早防、早诊、早治。寻求肿瘤标志物是目前肿瘤早期诊断常用的方法。本文就前列腺特异性抗原(prostatespecific antigen,PSA)和新发现的几种相关肿瘤标志物综述如下。1 PSAPSA是目前临床上广泛应用的检测指标,它是20世纪60年代末在研究免疫避孕过程中发现的。     

白光内镜联合超声内镜检查术在早期胃癌诊断中的应用价值

目的 分析早期胃癌患者经白光内镜联合超声内镜检查术（EUS）的病情评估情况。方法 回顾性分析2019年1月－2022年1月该院45例早期胃癌患者的临床资料，所有患者均完成白光内镜和EUS。分析早期胃癌不同形态病变的白光内镜特征，EUS和白光内镜对早期胃癌浸润深度的评估情况，早期胃癌在EUS和白光内镜下的T分期情况，白光内镜联合EUS在早期胃癌患者中的诊断结果。结果 45例早期胃癌患者的白光内镜结果显示，4例为隆起性，40例为平坦性，1例为凹陷性。以术后病理检查结果为金标准，EUS诊断早期胃癌T分期结果与病理检查结果有较高的一致性，白光内镜诊断早期胃癌T分期结果与病理检查结果一致性较低。白光内镜联合EUS诊断T_is期、T_1a期和T_1b期均具有较高的灵敏度、特异度和准确度。结论 白光内镜能够较好地评估早期胃癌患者的浸润深度，EUS可较好地评估病灶T分期情况，两者联合应用具有较高的诊断价值。     

引入靶区外扩预测放射治疗中危及器官自动分割的平均剂量偏差

目的 观察引入靶区外扩预测放射治疗(放疗)中自动分割危及器官(OAR)的平均剂量偏差的价值。方法 将100例接受放疗的直肠癌患者随机分为训练集(n=30)和测试集(n=70)。对训练集手动分割CT图中的靶区,之后分别对膀胱、小肠和双侧股骨头4个OAR进行手动和自动分割。根据自动分割的OAR设计放疗计划,得到对应的剂量分布;利用Python程序统计每个OAR与靶区外扩环重叠区域内的剂量平均值,以之作为代表剂量,用于预测测试集手动与自动分割平均剂量的差异,比较预测平均剂量与实际平均剂量的差异。再次随机将100例分为训练集、测试集各50例,重复上述过程。结果 首次预测显示,测试集70例中,69例膀胱预测与实际剂量差异均<0.5 Gy,69例小肠预测与实际剂量差异均<3 Gy,全部70例双侧股骨头预测与实际剂量差异均<0.5 Gy;对于膀胱、小肠和左、右侧股骨头,预测与实际平均剂量差异的一致性相关系数(CCC)分别为0.96、0.86、0.81和0.69。第2次预测显示,测试集50例中,46例膀胱的预测与实际剂量差异均<0.5 Gy,49例小肠的预测和实际剂量差异均<3 Gy,所有病例双侧股骨头的预测和实际剂量差异均<0.5 Gy;对于膀胱、小肠和左、右侧股骨头,预测与实际平均剂量差异的CCC分别为0.97、0.90、0.82和0.78。结论 引入靶区外扩可有效预测直肠癌放疗中自动分割OAR产生的剂量偏差。